PMID- 21228102
OWN - NLM
STAT- MEDLINE
DCOM- 20110701
LR  - 20220330
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 300
IP  - 5
DP  - 2011 May
TI  - GSK3beta inactivation in podocytes results in decreased phosphorylation of p70S6K 
      accompanied by cytoskeletal rearrangements and inhibited motility.
PG  - F1152-62
LID - 10.1152/ajprenal.00373.2010 [doi]
AB  - The inhibition of mTOR kinase after renal transplantation has been associated 
      with podocyte injury and proteinuria; however, the signaling pathways regulating 
      these effects are not well understood. We found that prolonged rapamycin 
      treatment in podocytes leads to an increase in glycogen synthase kinase 3beta 
      (GSK3beta) phosphorylation, resulting in inactivation of total GSK3beta kinase 
      activity. To investigate the cellular consequences of the inactivation of GSK3beta, 
      we used two inhibitors reducing kinase activity and studied the cross talk 
      between GSK3 function and the Akt/mammalian target of rapamycin (mTOR) pathway. 
      Both GSK3 inhibitors reduced the phosphorylation of the mTOR downstream target, 
      p70(S6K), indicating that GSK3 inhibition in podocytes is able to cause similar 
      effects as treatment with rapamycin. Moreover, GSK3 inhibition was accompanied by 
      the reduced expression of slit diaphragm-associated proteins and resulted in an 
      altered cytoskeletal structure and reduced motility of podocytes, suggesting that 
      GSK3 kinase can modulate Akt/mTOR-dependent signaling in podocytes.
FAU - George, Britta
AU  - George B
AD  - Medizinische Klinik und Poliklinik D, Molekulare Nephrologie, 
      Universitatsklinikum Munster, Germany.
FAU - Vollenbroker, Beate
AU  - Vollenbroker B
FAU - Saleem, Moin A
AU  - Saleem MA
FAU - Huber, Tobias B
AU  - Huber TB
FAU - Pavenstadt, Hermann
AU  - Pavenstadt H
FAU - Weide, Thomas
AU  - Weide T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110112
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CD2-associated protein)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Indoles)
RN  - 0 (Maleimides)
RN  - 0 (Membrane Proteins)
RN  - 0 (NIN protein, human)
RN  - 0 (Nck protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (SB 216763)
RN  - 0 (WT1 Proteins)
RN  - 0 (nephrin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - G4962QA067 (Lithium Chloride)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Cell Line
MH  - Cell Movement/*drug effects
MH  - Cytoskeletal Proteins/*antagonists & inhibitors/metabolism
MH  - Cytoskeleton/*drug effects/enzymology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Indoles/pharmacology
MH  - Lithium Chloride/pharmacology
MH  - Maleimides/pharmacology
MH  - Membrane Proteins/metabolism
MH  - Nuclear Proteins/*antagonists & inhibitors/metabolism
MH  - Oncogene Proteins/metabolism
MH  - Phosphorylation
MH  - Podocytes/*drug effects/enzymology
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Time Factors
MH  - WT1 Proteins/metabolism
EDAT- 2011/01/14 06:00
MHDA- 2011/07/02 06:00
CRDT- 2011/01/14 06:00
PHST- 2011/01/14 06:00 [entrez]
PHST- 2011/01/14 06:00 [pubmed]
PHST- 2011/07/02 06:00 [medline]
AID - ajprenal.00373.2010 [pii]
AID - 10.1152/ajprenal.00373.2010 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2011 May;300(5):F1152-62. doi: 
      10.1152/ajprenal.00373.2010. Epub 2011 Jan 12.